1. Technical Field
The present invention provides a process for synthesizing a compound of the following Formula (D), which is an important intermediate for manufacturing activated blood coagulation factor Xa (FXa) inhibitor, Edoxaban. The said process is simple and can be used as an industrial process

2. Description of Related Art
Activated blood coagulation factor Xa (FXa) inhibitor, Edoxaban, can block harmful effects and be used as an effective compound for preventing and/or treating thromboembolism, which is a compound of the following Formula (1), N1-(5-chloropyridin-2-yl)-N2-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide:

The compound of the following formula (D), tert-butyl (1R,2S,5S)-2-({2-[(5-chloropyridin-2-yl)amino]-2-oxoacetyl}amino)-5-(dimethylaminocarbonyl)cyclohexylcarbamate, is a known intermediate compound for manufacturing the compound of Formula (1). PCT laid-open patent application no. WO 2003/000657 (also published as JP2001-187105A and U.S. Pat. No. 7,365,205B2) disclosed a process for synthesizing compound of Formula (D), which comprises: treating a compound of the following formula (C), ethyl 2-[(5-chloropyridin-2-yl)amino]-2-oxoacetate monohydrochloride, from its ethyl ester to obtain lithium compound;
added a compound represented by the following formula (A) as tert-butyl {(1R,2S,5S)-2-amino-5-[(dimethylamino)carbonyl]cyclohexyl}carbamate, hydroxybenzotriazole monohydrate, and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride to the mixture of the lithium compound in dichloromethane and reacted; and then purified by column chromatography on silica gel to obtain the compound of Formula (D)

PCT laid-open patent application no. WO 2007/032498 (also published as JP2007-106759A and U.S. Pat. No. 8,686,189B2) disclosed a process for synthesizing the compound of formula (D), which comprises: adding the oxalate of compound of formula (A) into excessive amount of tertiary amines for neutralizing the salt of thereof; and then adding the compound of formula (C) to the mixture.
PCT laid-open patent application no. WO 2010/104078 (also published as U.S. Pat. No. 8,357,808B2) claims a similar process to the above patents, characterized in treating the compound of formula (C) with tertiary amines in C2-C4 nitriles solvent and then adding the oxalate of compound of formula (A) to the mixture.